LIPID-PEROXIDATION AND FORMATION OF 8-HYDROXYDEOXYGUANOSINE FROM ACUTE DOSES OF HALOGENATED ACETIC-ACIDS

Chlorinated, brominated, and mixed bromochloro acetates are major by-p roducts of water disinfection by chlorine or ozone. The chlorinated ac etates, trichloroacetate (TCA) and dichloroacetate (DCA), are carcinog enic in rodents. Brominated analogs of TCA and DCA have received littl e study. TCA and DCA induce lipid peroxidation in the livers of rodent s when administered acutely. Oxidative stress can also result in oxida tive damage to DNA, most commonly measured as increases in 8-hydroxyde oxyguanosine (8-OHdG) adducts. In this study, the ability of acute dos es of TCA, DCA, dibromoacetate (DBA), bromodichloroacetate (BDCA), and bromochloroacetate (BCA) to induce lipid peroxidation and 8-OHdG form ation was examined. Male B6C3F1 mice developed significant increases i n 8-OHdG/dG ratios in nuclear DNA isolated from livers when treated wi th haloacetates. The extent of 8-OHdG formation appeared to be related to the ability to induce thiobarbituric acid-reactive substances (TEA RS). The order of potency was DEA congruent to BCA > BDCA > DCA > TCA. The induction of 8-OHdG was found to be generally more sensitive to t reatment with haloacetates than the TEARS response. Significantly elev ated levels of 8-OHdG were observed at doses of DEA, BCA, and BDCA as low as 30 mg/kg. We suggest that formation of 8-OHdG by brominated hal oacetates may contribute to their toxicological effects. (C) 1996 Soci ety of Toxicology